Hiroki Kuroda

Postoperative Cerebral White Matter Damage Associated with Cerebral Hyperperfusion and Cognitive Impairment after Carotid Endarterectomy: A Diffusion Tensor Magnetic Resonance Imaging Study

Background: Cerebral hyperperfusion after carotid endarterectomy (CEA), even when asymptomatic, often impairs cognitive function. However, conventional magnetic resonance (MR) imaging rarely demonstrates structural brain damage associated with postoperative cognitive impairment. MR diffusion tensor imaging (DTI) is potentially more sensitive for detection of white matter damage. Among the common parameters derived by DTI, fractional anisotropy (FA) is a marker of tract integrity, and mechanical disruption of axonal cylinders and loss of continuity of myelin sheaths may be responsible for reduced FA in white matter. The purpose of the present study was to determine whether postoperative cerebral white matter damage that can be detected by FA derived by DTI is associated with cerebral hyperperfusion after CEA and correlates with postoperative cognitive impairment. Methods: In 70 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA and on postoperative day 3. FA values in cerebral white matter were assessed using DTI before and 1 month after surgery. These values were normalized and analyzed using statistical parametric mapping 5. In each corresponding voxel in the pre- and postoperative normalized FA maps of each patient, a postoperative FA value minus a preoperative FA value was calculated, and a voxel with postoperatively reduced FA was defined based on data obtained from healthy volunteers. The number of voxels with postoperatively reduced FA was calculated and defined as the volume with postoperatively reduced FA. Neuropsychological testing, consisting of the Wechsler Adult Intelligence Scale Revised, the Wechsler Memory Scale and the Rey-Osterreith Complex Figure test, was also performed preoperatively and after the first postoperative month. Postoperative cognitive impairment on neuropsychological testing in each patient was defined based on data obtained from patients with asymptomatic unruptured cerebral aneurysms. Results: Post-CEA hyperperfusion on brain perfusion SPECT (CBF increase ≥100% compared with preoperative values) and postoperative cognitive impairment on neuropsychological testing were observed in 11 (16%) and 9 patients (13%), respectively. The volume with postoperatively reduced FA in cerebral white matter ipsilateral to surgery was significantly greater in patients with post-CEA hyperperfusion than in those without (p < 0.0001). This volume in cerebral white matter ipsilateral to surgery was also significantly associated with postoperative cognitive impairment (95% confidence interval, 1.559–8.853; p = 0.0085). Conclusions: Cerebral hyperperfusion after CEA results in postoperative cerebral white matter damage that correlates with postoperative cognitive impairment.

PREDICTION OF CEREBRAL HYPERPERFUSION AFTER CAROTID ENDARTERECTOMY USING MIDDLE CEREBRAL ARTERY SIGNAL INTENSITY IN PREOPERATIVE SINGLE-SLAB 3-DIMENSIONAL TIME-OF-FLIGHT MAGNETIC RESONANCE ANGIOGRAPHY

OBJECTIVECerebral hyperperfusion after carotid endarterectomy (CEA) occurs in patients with preoperative impairments in cerebral hemodynamics. Signal intensity of the middle cerebral artery (MCA) on single-slab 3-dimensional time-of-flight magnetic resonance angiography (MRA) can assess hemodynamic impairment in the cerebral hemisphere. The purpose of the present study was to determine whether the signal intensity of the MCA on preoperative MRA could identify patients at risk for cerebral hyperperfusion after CEA. METHODSThe signal intensity of the MCA ipsilateral to CEA on preoperative MRA was graded according to the ability to visualize the MCA in 81 patients with ipsilateral internal carotid artery stenosis (≥70%). Cerebral blood flow was also quantified using single-photon emission computed tomography before and immediately after CEA and on the third postoperative day. RESULTSCerebral hyperperfusion immediately after CEA (cerebral blood flow increase ≥100% compared with preoperative values) was observed in 10 patients. Multivariate analysis revealed that only reduced signal intensity of the MCA was significantly associated with the development of postoperative cerebral hyperperfusion (95% confidence interval, 1.015–1.401; P = 0.0319). When the reduced signal intensity of the MCA on MRA was defined as an impairment in cerebral hemodynamics, MRA grading resulted in 100% sensitivity and 63% specificity, with a 28% positive predictive value and a 100% negative predictive value for the development of post-CEA hyperperfusion. Hyperperfusion syndrome developed on the fourth and sixth postoperative days in 2 of the 10 patients who exhibited hyperperfusion immediately after CEA. CONCLUSIONSignal intensity of the MCA, as assessed by this simple MRA method, may identify patients at risk for post-CEA cerebral hyperperfusion.

Central benzodiazepine receptor binding potential and CBF images on SPECT correlate with oxygen extraction fraction images on PET in the cerebral cortex with unilateral major cerebral artery occlusive disease.

Oxygen extraction fraction (OEF) is a key predictor of stroke recurrence in patients with symptomatic major cerebral arterial occlusive disease. The purpose of the present study was to compare central benzodiazepine receptor binding potential (BRBP) and cerebral blood flow (CBF) images on SPECT with OEF images on PET in patients with chronic unilateral middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive disease. Methods: OEF, CBF, and BRBP were assessed using 15O PET and N-isopropyl-p-123I-iodoamphetamine and 123I-iomazenil SPECT, respectively, in 20 healthy subjects and in 34 patients with unilateral MCA or ICA occlusive disease. All images were transformed into the standard brain size and shape by linear and nonlinear transformation using statistical parametric mapping for anatomic standardization. A region of interest (ROI) was automatically placed according to the arterial supply using a 3-dimensional stereotactic ROI template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. Results: Among patients with occlusive disease, a significant positive correlation was observed between PET OEF and SPECT BRBP/CBF ratios in 3 cerebral cortical regions (r = 0.851, P < 0.0001, for anterior cerebral artery [ACA] ROI; r = 0.807, P < 0.0001, for MCA ROI; and r = 0.774, P < 0.0001, for posterior cerebral artery [PCA] ROI), but there were no correlations between these 2 parameters in the basal ganglia or the cerebellum. When an abnormally elevated PET OEF ratio was defined as a value greater than the mean + 2 SDs obtained in healthy subjects, sensitivity and specificity were, respectively, 100% and 96% for the ACA ROI, 100% and 89% for the MCA ROI, and 100% and 93% for the PCA ROI for the SPECT BRBP/CBF ratio for detecting an abnormally elevated PET OEF ratio. Conclusion: BRBP/CBF images on SPECT correlate with OEF images on PET in a specific clinical setting—that is, in the cerebral cortex of patients with chronic unilateral MCA or ICA occlusive disease.

Intentional Hypertension During Dissection of Carotid Arteries in Endarterectomy Prevents Postoperative Development of New Cerebral Ischemic Lesions Caused by Intraoperative Microemboli

BACKGROUND:Low blood flow velocity in the middle cerebral artery (MCA) correlates with the development of postoperative cerebral ischemic lesions related to generation of microemboli during dissection of carotid arteries in carotid endarterectomy (CEA). OBJECTIVE:The purpose of this prospectively controlled trial was to determine whether increased mean blood flow velocity in the MCA by intentional hypertension during carotid dissection in CEA prevented postoperative development of new cerebral ischemic lesions caused by intraoperative microemboli. METHODS:Patients with ipsilateral internal carotid artery stenosis (>70%) underwent CEA under transcranial Doppler monitoring of mean blood flow velocity and microembolic signals in the ipsilateral MCA. Attempts were made to keep systolic blood pressure during carotid dissection between −10% and +10% of the preoperative value (controls, n = 65) or above a +10% increase (intentional hypertension group, n = 65). RESULTS:Incidence of new ischemic lesions on postoperative diffusion-weighted magnetic resonance imaging was significantly lower in the intentional hypertension group both for all patients (controls, 15.4%; intentional hypertension group, 3.1%; P = .03) and in a subgroup of 37 patients showing microembolic signals during carotid dissection (controls, 52.6%; intentional hypertension group, 11.1%; P = .013). Logistic regression analysis demonstrated the absence of intentional hyperperfusion (95% confidence interval: 1.77-100.00; P = .012) and high number of microembolic signals (95% confidence interval: 1.00-1.62; P = .05) during carotid dissection were significant independent predictors of the postoperative development of new ischemic lesions on diffusion-weighted magnetic resonance imaging. CONCLUSION:Increased MCA mean blood flow velocity by intentional hypertension during dissection of the carotid artery in CEA prevents the postoperative development of new cerebral ischemic lesions caused by intraoperative microemboli.

Accuracy of central benzodiazepine receptor binding potential/cerebral blood flow SPECT imaging for detecting misery perfusion in patients with unilateral major cerebral artery occlusive diseases: comparison with cerebrovascular reactivity to acetazolamide and cerebral blood flow SPECT imaging.

Purpose: The aim of the present study was to determine whether central benzodiazepine receptor binding potential (BRBP)/cerebral blood flow (CBF) or a combination of CBF and cerebrovascular reactivity (CVR) to acetazolamide on single-photon emission computed tomography (SPECT) more accurately detects misery perfusion, indicating elevation of absolute value of oxygen extraction fraction (OEF) on positron emission tomography (PET), in patients with unilateral major cerebral artery occlusive diseases. Methods: In 84 patients, OEF, CBF, CVR to acetazolamide, and BRBP were assessed using 15O-PET and N-isopropyl-p-[123I]-iodoamphetamine and [123I]-iomazenil SPECT, respectively. A region of interest was automatically placed in the middle cerebral artery territory using a 3-dimensional stereotactic region of interest template. Results: Sensitivity, specificity, and positive and negative predictive values for the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF to detect the abnormally elevated PET-OEF in the affected hemisphere were 100%, 86.4%, 66.7%, and 100%, respectively. Area under the receiver operating characteristic curve in detecting the abnormally elevated PET-OEF in the affected hemisphere did not differ between analysis of the combination of SPECT-CBF and SPECT-CVR in the affected hemisphere (0.89; 95% confidence interval, 0.80–0.94) and that of the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF (0.93; 95% confidence interval, 0.86–0.97). The combination of the 3 detected abnormally elevated PET-OEF with 97.0% specificity and 90.0% positive predictive value. Conclusions: The accuracy of central BRBP/CBF asymmetry on SPECT is equivalent to that of the combination of CBF and CVR to acetazolamide on SPECT for detecting misery perfusion in patients with unilateral major cerebral artery occlusive disease.

Effect of combination therapy with the angiotensin receptor blocker losartan plus hydrochlorothiazide on brain perfusion in patients with both hypertension and cerebral hemodynamic impairment due to symptomatic chronic major cerebral artery steno-occlusive disease: a SPECT study.

Background: While the combination of an angiotensin receptor blocker with thiazide diuretics produces a clinically beneficial reduction in blood pressure in patients who otherwise only partially respond to monotherapy with an angiotensin receptor blocker, blood pressure-lowering therapy with combination antihypertensive drug regimens in patients with cerebral hemodynamic impairment may adversely affect cerebral hemodynamics. The purpose of the present exploratory study was to determine whether blood pressure-lowering therapy with the combination of the angiotensin receptor blocker losartan plus hydrochlorothiazide (LPH) worsens brain perfusion in patients with both hypertension and cerebral hemodynamic impairment due to symptomatic chronic major cerebral artery steno-occlusive disease. Methods: Patients with losartan-resistant hypertension and reduced cerebrovascular reactivity (CVR) to acetazolamide due to symptomatic chronic internal carotid artery (ICA) or middle cerebral artery (MCA) steno-occlusive disease were prospectively entered into the present study and received 50 mg/day of losartan plus 12.5 mg/day of hydrochlorothiazideat 14 weeks after the last ischemic event. Cerebral blood flow (CBF) and CVR were measured before and 12 weeks after initiating LPH using N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography (SPECT). A region of interest (ROI) was automatically placed in the MCA territory on each SPECT image using a three-dimensional stereotactic ROI template. Results: None of the 18 patients who participated in the study experienced any new neurological symptoms or adverse effects related to antihypertensive drugs. Systolic (p < 0.001) and diastolic (p < 0.001) blood pressures were significantly reduced after the administration of LPH, with average reductions of 11 mm Hg in systolic blood pressure and 10 mm Hg in diastolic blood pressure. While in the affected hemisphere CBF did not differ between measurements taken before and after the administration of LPH, CVR was significantly higher after the administration of LPH than before (p = 0.007) and was significantly improved in 5 of 18 patients. In the contralateral hemisphere, CBF and CVR did not differ between measurements taken before and after the administration of LPH. There were no patients who experienced a significant deterioration in CBF or CVR in the affected or contralateral hemisphere after the administration of LPH. Conclusions: Although the present study was exploratory and its results were preliminary due to the small sample size, the current data suggest that blood pressure-lowering therapy with LPH apparently does not result in worsening of cerebral hemodynamics in patients with both hypertension and cerebral hemodynamic impairment due to symptomatic chronic ICA or MCA steno-occlusive disease.

Preoperative Central Benzodiazepine Receptor Binding Potential and Cerebral Blood Flow Images on SPECT Predict Development of New Cerebral Ischemic Events and Cerebral Hyperperfusion After Carotid Endarterectomy

Risk factors for cerebrovascular complications developing during or after carotid endarterectomy (CEA) include preoperative impairments in cerebral hemodynamics, as detected by the demonstration of decreased cerebrovascular reactivity (CVR) to acetazolamide on brain perfusion SPECT. Central benzodiazepine receptor binding potential (CBRBP) and cerebral blood flow (CBF) images on SPECT provide high sensitivity and high specificity for detecting misery perfusion in patients with chronic unilateral major cerebral artery occlusive disease. The aim of the present study was to determine whether preoperative CBRBP/CBF images on SPECT could identify patients at risk for new cerebral ischemic events, including neurologic deficits and cerebral ischemic lesions on diffusion-weighted MRI, or cerebral hyperperfusion after CEA and to compare the predictive accuracy of CBRBP/CBF with that of CVR to acetazolamide on SPECT. Methods: CBF, CVR, and CBRBP were assessed using N-isopropyl-p-123I-iodoamphetamine (123I-IMP) and 123I-iomazenil SPECT before CEA in 112 patients with unilateral internal carotid artery stenosis (≥70%). CBF measurement using 123I-IMP SPECT was also performed immediately and 3 d after CEA. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a 3-dimensional stereotactic region-of-interest template. Diffusion-weighted MRI was performed within 3 d before and 24 h after surgery. Results: A preoperative increase in the affected side–to–contralateral side asymmetry on CBRBP/CBF value was the only significant independent predictor of postoperative new cerebral ischemic events (95% confidence intervals [CI], 1.145–1.608; P = 0.0004) or post-CEA hyperperfusion (95% CI, 1.244–2.252; P = 0.0007). There was no difference in the ability to predict post-CEA hyperperfusion when comparing the area under the receiver-operating-characteristic curve of the affected side–to–contralateral side asymmetry on CBRBP/CBF and that of the CVR in the affected hemisphere. However, the former value (0.924; 95% CI, 0.854–0.972) was significantly greater than the latter value (0.782; 95% CI, 0.697–0.852) for the prediction of new postoperative cerebral ischemic events (P < 0.05). Conclusion: Preoperative CBRBP/CBF images on SPECT can more accurately identify patients at risk for cerebrovascular complications occurring during or after CEA when compared with preoperative CVR to acetazolamide.

Comparison of early and late images on 123I-iomazenil SPECT with cerebral blood flow and oxygen extraction fraction images on PET in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease.

ObjectiveThe aim of the present study was to determine whether early and late/early images on 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) correlate with cerebral blood flow (CBF) images and oxygen extraction fraction (OEF) images on PET, respectively, in the cerebral cortex of patients with chronic unilateral middle cerebral artery or internal carotid artery occlusive disease. MethodsIn 20 normal individuals and in 68 patients, CBF and OEF were assessed using 15O-PET, and brain SPECT scans were initiated immediately after (early images) and 180 min after (late images) the administration of 123I-IMZ. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a three-dimensional stereotaxic region of interest template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. ResultsAmong patients, a significant positive correlation was observed between PET-CBF ratios and the SPECT-early IMZ ratios (r=0.797, P<0.0001) as well as between the PET-OEF ratios and the SPECT-late/early IMZ ratios (r=0.679, P<0.0001). When an abnormally elevated PET-OEF ratio was defined as a value greater than the mean+2 SD obtained in normal participants, the SPECT-late/early IMZ ratios yielded 100% sensitivity and 93% specificity, with 76% positive-predictive and 100% negative-predictive values for detecting abnormally elevated PET-OEF ratios. ConclusionEarly and late/early images on 123I-IMZ SPECT correlate with CBF images and OEF images on PET, respectively, in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease.

Spontaneous recovery of reduced cortical central benzodiazepine receptor binding potential on I-123 Iomazenil SPECT in a patient with status epilepticus.

Abstract: A reduction in cortical benzodiazepine receptor binding potential on late images of I-123 iomazenil SPECT indicates irreversible neural damage or loss. We present the case of a 26-year-old woman with status epilepticus in whom SPECT imaging using I-123 iomazenil and I-123 N-isopropyl-p-iodoamphetamine 7 and 9 days after the last seizure, respectively, demonstrated reduction in central benzodiazepine receptor binding potential with hyperperfusion in the affected cerebral hemisphere and crossed cerebellar hypoperfusion. However, 3 months later, repeat studies showed resolution of the reduction in cortical benzodiazepine receptor binding potential, resolution of hyperperfusion, and resolution of crossed cerebellar hypoperfusion.

Early onset of PRES in a patient with a subarachnoid haemorrhage due to a ruptured intracranial aneurysm.

Abstract Posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid haemorrhage (SAH). We present a case involving a patient who developed PRES, prior to induction of hypertensive therapy, 2 days after the onset of a SAH due to a ruptured intracranial aneurysm.